Journal of Translational Medic<strong>in</strong>e 2008, 6:13http://www.translational-medic<strong>in</strong>e.com/content/6/1/13Norwegian Cancer Society (grant A95068, RAL). The study is also supportedby grants from the Norwegian Research Council (163962/V50, RAL<strong>and</strong> 161448/V40, RAL). MAA is supported by grants from the M<strong>in</strong>isterio deEducación y Ciencia (BFU2006-01925; GEN2003-20662-C07-02).Lack of MAL prote<strong>in</strong> expression <strong>in</strong> colorectal carc<strong>in</strong>omasFigure 6Lack of MAL prote<strong>in</strong> expression <strong>in</strong> colorectal carc<strong>in</strong>omas.Positive cytoplasmic sta<strong>in</strong><strong>in</strong>g of MAL was found <strong>in</strong>kidney tubuli (A), <strong>and</strong> <strong>no</strong> sta<strong>in</strong><strong>in</strong>g was observed <strong>in</strong> heart muscle(B), <strong>in</strong> agreement with earlier reports [30]. The epithelialcells of colorectal carc<strong>in</strong>omas were MAL negative (C, D),whereas <strong>in</strong> <strong>no</strong>rmal colon tissue, cytoplasmic expression ofMAL was found <strong>in</strong> both epithelia <strong>and</strong> connective tissue (E, F).All images were captured us<strong>in</strong>g the 40× lens (400× magnification).colon cancer cell l<strong>in</strong>es with epi<strong>genetic</strong> drugs. MAA providedthe antibody for immu<strong>no</strong>histochemical analyses<strong>and</strong> contributed with scientific discussion. AK providedseveral of the cancer cell l<strong>in</strong>es. GIM <strong>and</strong> TOR have collectedthe series of human primary carc<strong>in</strong>omas <strong>and</strong> <strong>no</strong>rmalmucosa tissue <strong>and</strong> provided all cl<strong>in</strong>ical <strong>and</strong>pathological <strong>in</strong>formation regard<strong>in</strong>g these samples. RISgenerated the tissue microarray <strong>and</strong> contributed <strong>in</strong> manuscriptpreparations. ETE has provided the series of ade<strong>no</strong>masamples <strong>and</strong> provided all cl<strong>in</strong>ical <strong>and</strong> pathological<strong>in</strong>formation regard<strong>in</strong>g these samples <strong>and</strong> contributed <strong>in</strong>manuscript preparations. RAL conceived the study, participated<strong>in</strong> its design, contributed <strong>in</strong> evaluation of results,scientific discussion <strong>and</strong> <strong>in</strong> manuscript preparation. Allauthors have read <strong>and</strong> approved the f<strong>in</strong>al manuscript.Ack<strong>no</strong>wledgementsWe are grateful to Vera M. Abeler for evaluat<strong>in</strong>g the immu<strong>no</strong>histochemicalsta<strong>in</strong><strong>in</strong>g of the TMA tissue cores <strong>and</strong> to St<strong>in</strong>e Aske Danielsen for technicalassistance. GEL is a post doc <strong>and</strong> MB is a PhD student supported by theReferences1. Fe<strong>in</strong>berg AP, Ohlsson R, Henikoff S: The epi<strong>genetic</strong> progenitororig<strong>in</strong> of human cancer. Nat Rev Genet 2006, 7:21-33.2. Kane MF, Loda M, Gaida GM, Lipman J, Mishra R, Goldman H, JessupJM, Kolodner R: Methylation of the hMLH1 promoter correlateswith lack of expression of hMLH1 <strong>in</strong> sporadic colontumors <strong>and</strong> mismatch repair-defective human tumor celll<strong>in</strong>es. Cancer Res 1997, 57:808-811.3. 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J Natl Cancer Inst 2003, 95:1747-1757.Publish with BioMed Central <strong>and</strong> everyscientist can read your work free of charge"BioMed Central will be the most significant development fordissem<strong>in</strong>at<strong>in</strong>g the results of biomedical <strong>research</strong> <strong>in</strong> our lifetime."Sir Paul Nurse, Cancer Research UKYour <strong>research</strong> papers will be:available free of charge to the entire biomedical communitypeer reviewed <strong>and</strong> published immediately upon acceptancecited <strong>in</strong> PubMed <strong>and</strong> archived on PubMed Centralyours — you keep the copyrightSubmit your manuscript here:http://www.biomedcentral.com/<strong>in</strong>fo/publish<strong>in</strong>g_adv.aspBioMedcentralPage 11 of 11(page number <strong>no</strong>t for citation purposes)
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Novel genetic and epigenetic altera
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TABLE OF CONTENTSACKNOWLEDGEMENTS .
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ACKNOWLEDGEMENTSThe present work ha
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Prefacetechnology[3]. This new tech
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SummaryThe subgroup of carcinomas w
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Introduction“Epigenetic inheritan
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Introductionamino acid change it is
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Introductionmethylation during embr
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IntroductionDNA is most of the time
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IntroductionFigure 5. DNA methylati
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IntroductionFigure 6. Incidence rat
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IntroductionFigure 8. Tumor staging
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Introductioninasmuch as 80% of colo
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IntroductionInstabilities involved
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Introductionthere seems to be a fid
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Introductionsevere alterations are
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Introductionpopulation-wide screeni
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IntroductionFigure 12. Present and
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RESULTS IN BRIEFPaper Ia. “DNA hy
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Results in Briefinstability, and se
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Results in BriefUnivariate survival
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Discussionseveral factors, and full
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Discussionlow threshold, we increas
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DiscussionIt may seem like unnecess
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Discussionthan 96% DHPLC do not sta
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- Page 60 and 61: DiscussionThese examples underline
- Page 62 and 63: Discussiongenes. One is based on mu
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- Page 66 and 67: Future PerspectivesMolecular risk a
- Page 68 and 69: REFERENCES1. Breasted J (1930) The
- Page 70 and 71: References29. Deng G, Chen A, Pong
- Page 72 and 73: References57. Al-Sukhni W, Aronson
- Page 74 and 75: References84. Kunkel TA (1993) Nucl
- Page 76 and 77: ReferencesLeggett B, Levine J, Kim
- Page 78 and 79: References133. Lind GE, Thorstensen
- Page 80 and 81: References156. Meling GI, Lothe RA,
- Page 82 and 83: ReferencesT, Song X, Day RH, Sledzi
- Page 84 and 85: References196. Honda S, Haruta M, S
- Page 86 and 87: ORIGINAL ARTICLESAPPENDIXAppendix I
- Page 89 and 90: GASTROENTEROLOGY 2007;132:1631-1639
- Page 91: Paper IbGuro E Lind, Terje Ahlquist
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- Page 108 and 109: BackgroundMost cases of colorectal
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entering M-phase remains to be seen
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12. Duval A, Reperant M, Hamelin R
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34. Martineau-Thuillier S, Andreass
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AppendicesAppendix I:List of abbrev
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Critical Reviews TM in Oncogenesis,
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TARGET GENES OF MSI COLORECTAL CANC
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TARGET GENES OF MSI COLORECTAL CANC
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TARGET GENES OF MSI COLORECTAL CANC
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TARGET GENES OF MSI COLORECTAL CANC
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TARGET GENES OF MSI COLORECTAL CANC